Background: Testing for antibody to hepatitis B core antigen (anti-HBc) as a surrogate for hepatitis C viremia is no longer needed for blood donor screening. Currently, the important question is how much its use supplements hepatitis B surface antigen (HBsAg) donor screening in preventing transfusion-transmitted hepatitis B virus (HBV) infection. Study Design and Methods: In a study conducted ih the 1970s. 64 blood donors were associated with 15 cases of HBV (1.0%) in 1533 transfusion recipients. Sera from 61 donors at donation and 29 follow-up visits were available for present-day assays for HBsAg, HBV DNA, anti-HBc, and antibody to HBsAg (anti-HBs). Results: HBsAg was found in four previously negative blood donors; HBV DNA was limited to three of these four. Anti-HBc was detected In six HBsAg-negative donors. Two other donors were negative in all assays at donation, but positive for anti-HBc and anti-HBs 2 to 4 months later. The remaining donors were negative for all HBV markers which left five recipient cases unexplained: No HBV transmission was observed when anti-HBs sample-to-negative control values were greater than or equal to 10. Conclusion: Some 33 to 50 percent of cases of hepatitis B that could be transmitted by transfusion of blood from HBsAg-negative donors are prevented by anti-HBc screening. Anti-HBc-positive donors unequivocally positive for anti-HBs should be considered noninfectious for HBV and should be allowed td donate. Anti HBc screening of paid plasmapheresis donors, supplemented by anti-HBs testing, would reduce the amount of HBV to be processed by virus inactivation and increase the content of anti-HBs in plasma pools.